The increased number of cancer cases reported in the United States, and, indeed, around the world, is a major concern. Currently there are only a handful of treatments available for specific types of cancer, and these treatments require not only an early detection of the malignancy, but also a reliable assessment of the severity of the malignancy. Carcinoma of the prostate (PCA) is the most frequently diagnosed cancer in men in the United States, and is the second leading cause of male cancer deaths (Karp et al., 1996, Cancer Res. 56:5547-5556). Over 40,000 Americans are estimated to have died of PCA in 1995, and about 244,000 new cases of prostate cancer were detected (Cancer Facts and Figures—1995, American Cancer Society, Inc., 1995) and these numbers have increased annually at an alarming rate. Further, the rate of appearance of prostate cancer in African-American men is 37% higher than for their white counterparts (Jaroff, L. (Apr. 1, 1996), Time).
An unusual challenge presented by prostate cancer is that most prostate tumors do not represent life threatening conditions. Projections from autopsy surveys indicate that as many as 11 million American men have prostate cancer (Dhom, 1983, J. Cancer Res. Clin. Oncol., 106:210-218). Cancer cells are generally found in the prostates of men who live into their seventies or eighties. However not all of these men develop prostate cancer (PCA), and autopsies show microscopic clusters of prostate cancer cells in one-third of men who die of other causes (Thayer, W., (Mar. 19, 1996), quoted in Nutr. Act. Newsletter, 23(2):12). Death rates from prostate cancer rise after age 55, and new cases of prostate cancer, are increasing even faster than the death rate. These figures are consistent with clinical observations of prostate carcinomas, which normally exhibit a slow and lingering course of progression. Such disease progression results in relatively few prostate tumors developing into cases of clinical concern during the lifetime of the patient. If, upon detection with available methods, the cancer appears well-differentiated, organ-confined and focal, treatment normally cannot extend the life expectancy of older patients.
Unfortunately, prostate carcinomas that are progressive in nature frequently have already metastasized by the time of clinical detection with available methods. Survival rates for individuals with metastatic prostate cancer are quite low. Between these two extremes are patients with prostate tumors that will metastasize during their lifetimes, but have not yet done so. For these patients, surgical removal of the prostate is curative and extends life expectancy. Therefore, accurate determination of which group a newly diagnosed patient falls into is critical in determining optimal treatment and patient survival.
The current primary diagnostic tool for disorders of the prostate is measurement of the level of prostate-specific antigen (PSA) in blood, which in normal men ranges from 0 to 4 nanograms/milliliters. The presence of Prostate Specific Antigen (PSA) can be measured with relative ease from blood samples using standard antibody-based detection kits. Prostate enlargement, a condition known as benign prostatic hyperplasia (BPH), is found in about half of men over age 45. With BPH, PSA levels rise in proportion to prostate size, possibly obscuring diagnosis of PCA. In addition, a significant proportion of men with PCA have normal PSA levels. The PSA test is somewhat non-specific for distinguishing PCA and BPH, and produces a degree of false negative results (Garnick, M., (1993), Am. Inst. Med., 118:804-818). In the majority of cases, PSA elevation is due to BPH or prostatitis rather than carcinoma. The PSA test, a major advance over previous procedures, thus leaves much to be desired.
Although clinical and pathologic stage and histological grading systems (e.g., Gleason's) have been used to indicate prognosis for groups of patients based on the degree of tumor differentiation or the type of glandular pattern (Carter and Coffey, In: J. P. Karr and H. Yamanak (eds.), Prostate Cancer: The Second Tokyo Symposium, pp. 19-27, New York: Elsevier, 1989.; Diamond et al., J. Urol., 128: 729-734, 1982), these systems do not adequately predict the progression rate of the cancer. While the use of computer-system image analysis of histologic sections of primary lesions for “nuclear roundness” has been suggested as an aide in the management of individual patients (Diamond et al., 1982, J. Urol., 128:729-734), this method is of limited use in studying the progression of the disease.
There currently is a need for new methods in the fight against prostate cancer and it would therefore be beneficial to provide specific methods and reagents for the diagnosis, staging, prognosis, and monitoring of prostate cancer.